effect of anti-diabetic drugs on bone metabolism and glycemic variability

Conditions: Type 2 Diabetes Mellitus; Menopause; Osteoporosis; Osteopenia

Summary: this is a monocentric, prospective, randomized, open-label, comparative, phase iv study, to compare the effects of vildagliptin and gliclazide mr on markers of bone remodeling, bone mineral density and glycemic variability in postmenopausal women with type 2 diabetes. a total of 38 women with documented type 2 diabetes and menopause will be enrolled. the active treatment will include a 50 mg dose of vildagliptin od twice a day. as comparator, gliclazide mr will be administered at a dose of 60 to 120 mg od once a day.

this is a monocentric, prospective, randomized, open-label, comparative, phase iv study, to compare the effects of vildagliptin and gliclazide mr on markers of bone remodeling, bone mineral density and glycemic variability in postmenopausal women with type 2 diabetes. target population of clinical trial subjects a total of 38 women with documented type 2 diabetes and menopause will be enrolled. to be as close to a real life scenario as possible, clinical trial subjects which are treated with glucose-lowering medication (except incretin or sulfonylurea based therapies) and treatment-naive subjects will be included. investigational product, posology and method of administration the active treatment will include a 50 mg dose of vildagliptin od twice a day. comparator, posology and method of administration as comparator, gliclazide mr will be administered at a dose of 60 to 120 mg od once a day. treatment duration the study will have an expected total duration of 18 months, 12 months of active treatment.

Eligibility criteria:
inclusion criteria: * informed consent form obtained before any study-related activity. study-related activities are any procedure that would not be performed during the normal treatment of the patient. * all study subjects must be women diagnosed with type 2 diabetes based on current guidelines of sociedade brasileira de diabetes (sbd - brazilian society of diabetes) and/or american society of diabetes (ada) and they should have all the following criteria: * age ≥ 40 years old. * hba1c ≥ 6.5% at randomization. * menopause defined as: * absence of menstruation for at least 12 months in patients with an intact uterus, or * fsh level greater than 30 miu/ml in a hysterectomized patient and/or, * fsh level greater than 30 miu/ml in a patient with surgical menopause. exclusion criteria: * acute vascular event (cardiac, cerebral or peripheral) for at least 2 months of randomization. * patient on chronic dialysis and/or renal transplantation and/or serum creatinine \> 1.5 mg/dl. * patients with hiv, severe autoimmune disease or chronic treatment with oral steroids (\> 30 consecutive days). * current or previous treatment (within 6 months) with incretin (dpp-iv inhibitor or glp-1 analog) within 6 months prior to randomization. * current or previous treatment with pioglitazone or rosiglitazone within 12 months prior to randomization. * sustained arterial hypertension \> 180/100 mm hg. * body mass index (bmi) \> 50 kg/m². * hba1c ≥ 9,5% at randomization. * transaminases (ast (sgot) and alt (sgpt)) \> 2.5 x upper limit of normal. * chronic liver disease or alcoholic liver disease. * ldl-cholesterol \> 250 mg/dl (\> 6.48 mmol/l). * triglycerides \> 1000 mg/dl (\> 11.3 mmol/l). * hdl-cholesterol \< 25 mg/dl (\< 0.64 mmol/l). * levels of 25-oh-vitamin d \< 20ng/ml at randomization * abnormal levels of pth, cortisol, igf-1 or gh at randomization * prescription of any investigational medication within one year before the screening visit (visit 1), unless there is a direct benefit to the study subject, at the discretion of the investigator. * history of previous fracture * pregnant or breastfeeding patients. * previous participation on this study. * individuals at risk for poor adherence to the protocol or medication. * any condition that makes the patient unable to complete the study within 12 months.

Keywords: diabetes type 2 diabetes mellitus osteopenia osteoporosis glycemic variability bone markers osteocalcin ntx ctx balp